tbuckley/cabot-search huggingface dataset:
Stiff Substrate Induces Nucleus Pulposus Cell Ferroptosis via YAP and N‐Cadherin Mediated Mechanotransduction
Authors: Wencan Ke, Zhiwei Liao, Huaizhen Liang, Bide Tong, Yu Song, Gaocai Li, Liang Ma, Kun Wang, Xiaobo Feng, Shuai Li, Wenbin Hua, Bingjin Wang, Cao Yang
Journal: Advanced Healthcare Materials (2023)

Increased tissue stiffness is associated with various pathological processes, such as fibrosis, inflammation, and aging. The matrix stiffness of the nucleus pulposus (NP) tissues increases gradually during intervertebral disc degeneration (IDD), while the mechanism through which NP cells sense and react to matrix stiffness remains unclear. In this study, the results indicate that ferroptosis is involved in stiff substrate-induced NP cell death. The expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) increases in NP cells of the stiff group, which mediates lipid peroxidation and ferroptosis in NP cells. In addition, stiff substrate activates the hippo signaling cascade and induces the nuclear translocation of yes-associated protein (YAP). Interestingly, inhibition of YAP is efficient to reverse the increase of ACSL4 expression caused by matrix stiffness. Furthermore, stiff substrate suppresses the expression of N-cadherin in NP cells. N-cadherin overexpression can inhibit YAP nuclear translocation via the formation of the N-cadherin/β-catenin/YAP complex, and reverse matrix stiffness-induced ferroptosis in NP cells. Finally, the effects of YAP inhibition and N-cadherin overexpression on IDD progression are further illustrated in animal models. These findings reveal a new mechanism of mechanotransduction in NP cells, providing novel insights into the development of therapies for the treatment of IDD.
Long-term Mortality in Individuals Diagnosed With Cancer During Pregnancy or Postpartum
Authors: Zoe F. Cairncross, Lorraine Shack, Gregg Nelson, Christine M. Friedenreich, Joel Ray, Deshayne B. Fell, Sarka Lisonkova, Parveen Bhatti, Khokan Sikdar, Carly McMorris, Amy Metcalfe
Journal: JAMA Oncology (2023)

Outcomes among patients with pregnancy-associated cancers (diagnosed during pregnancy or 1-year postpartum) other than breast cancer have received relatively little research attention. High-quality data from additional cancer sites are needed to inform the care of this unique group of patients.
Spatial and seasonal determinants of Lyme borreliosis incidence in France, 2016 to 2021
Authors: Wen Fu, Camille Bonnet, Alexandra Septfons, Julie Figoni, Jonas Durand, Pascale Frey-Klett, Denis Rustand, Benoît Jaulhac, Raphaëlle Métras
Journal: Eurosurveillance (2023)

Background Lyme borreliosis (LB) is the most widespread hard tick-borne zoonosis in the northern hemisphere. Existing studies in Europe have focused mainly on acarological risk assessment, with few investigations exploring human LB occurrence. Aim We explored the determinants of spatial and seasonal LB variations in France from 2016 to 2021 by integrating environmental, animal, meteorological and anthropogenic factors, and then mapped seasonal LB risk predictions. Methods We fitted 2016–19 LB national surveillance data to a two-part spatio-temporal statistical model. Spatial and temporal random effects were specified using a Besag-York-Mollie model and a seasonal model, respectively. Coefficients were estimated in a Bayesian framework using integrated nested Laplace approximation. Data from 2020–21 were used for model validation. Results A high vegetation index (≥ 0.6) was positively associated with seasonal LB presence, while the index of deer presence (&gt; 60%), mild soil temperature (15–22 °C), moderate air saturation deficit (1.5–5 mmHg) and higher tick bite frequency were associated with increased incidence. Prediction maps show a higher risk of LB in spring and summer (April–September), with higher incidence in parts of eastern, midwestern and south-western France. Conclusion We present a national level spatial assessment of seasonal LB occurrence in Europe, disentangling factors associated with the presence and increased incidence of LB. Our findings yield quantitative evidence for national public health agencies to plan targeted prevention campaigns to reduce LB burden, enhance surveillance and identify further data needs. This approach can be tested in other LB endemic areas.
Production of functional plasmacytoid dendritic cells – targeted chimeric antigen receptor T cells from patients with immune-mediated inflammatory diseases
Authors: Blandine Caël, Elodie Bôle-Richard, Jeanne  Galaine, Olivier Adotevi, Francine  Garnache-Ottou, François Aubin
Journal: British Journal of Dermatology (2023)

Our preliminary results demonstrate the feasibility of CAR123 production from the T cells of patients with autoimmune diseases and immune-mediated inflammatory diseases and their in vitro cytotoxicity towards circulating autologous plasmacytoid dendritic cells.
Representation of Racial and Ethnic Minorities in Nephrology Clinical Trials: A Systematic Review and Meta-Analysis
Authors: Qandeel H. Soomro, Angela McCarthy, Dalila Varela, Colin Keane, Javaughn Ways, Amalya M. Charytan, Giana Ramos, Joey Nicholson, David M. Charytan
Journal: Journal of the American Society of Nephrology (2023)

Significance statement Racial and ethnic disparities in clinical trial enrollment are well described. However, whether these disparities are present in nephrology randomized clinical trials has not been previously reported. We performed a systematic review and meta-analysis of 380 randomized clinical trials involving different aspects of kidney disease published between 2000 and 2021. Our results indicate that worldwide reporting of race and ethnicity is poor and that White individuals account for most of the randomized participants with decreased enrollment of Black participants in more recent trials. However, trials conducted in the United States have representation of Black and Hispanic participants consistent with the population prevalence of disease and under-representation of Asian participants. Background Under-representation of racial and ethnic minorities in clinical trials could worsen disparities, but reporting and enrollment practices in nephrology randomized clinical trials have not been described. Methods PubMed was searched to capture randomized clinical trials for five kidney disease–related conditions published between 2000 and 2021 in ten high-impact journals. We excluded trials with &lt;50 participants and pilot trials. Outcomes of interest were the proportion of trials reporting race and ethnicity and the proportions of enrolled participants in each race and ethnicity category. Results Among 380 trials worldwide, race was reported in just over half and ethnicity in 12%. Most enrolled participants were White, and Black individuals accounted for ≤10% of participants except in dialysis trials where they accounted for 26% of participants. However, Black participants were enrolled at high proportions relative to disease and population prevalence in US CKD, dialysis, and transplant trials representing 19% of participants in AKI, 26% in CKD, 44% in GN, 40% in dialysis, and 26% in transplant trials. Enrollment of Asian participants was low worldwide except in GN trials with marked under-representation in US CKD, dialysis, and transplant trials. Hispanic individuals represented only 13% of participants in US dialysis trials compared with 29% of US dialysis population. Conclusion More complete reporting of race and ethnicity in nephrology trials is needed. Black and Hispanic patients are well-represented in kidney disease trials in the United States. Asian patients are poorly represented in kidney trials both globally and in the United States.
FDA Approval Summary: Amivantamab for the Treatment of Patients with Non–Small Cell Lung Cancer with <i>EGFR</i> Exon 20 Insertion Mutations
Authors: Katie Chon, Erin Larkins, Somak Chatterjee, Pallavi S. Mishra-Kalyani, Stephanie Aungst, Emily Wearne, Sriram Subramaniam, Yangbing Li, Jiang Liu, Jielin Sun, Rosane Charlab, Hong Zhao, Banu Saritas-Yildirim, Rama Kamesh Bikkavilli, Soma Ghosh, Reena Philip, Julia A. Beaver, Harpreet Singh
Journal: Clinical Cancer Research (2023)

Abstract The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal–epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Approval was based on results of an ongoing, multicenter, nonrandomized, open-label, multicohort clinical trial (CHRYSALIS, NCT 02609776), demonstrating a substantial overall response rate (ORR) and durable responses, with an ORR of 40% [95% confidence interval (CI): 29–51] and a median response duration of 11.1 months (95% CI: 6.9–not evaluable). Guardant360 CDx was contemporaneously approved as a companion diagnostic for this indication to identify EGFR exon 20 insertion mutations in plasma specimens. The most notable safety finding was the high incidence (66%) of infusion-related reactions, which is addressed in both the Dosage and Administration and Warnings and Precautions sections of the product label. Other common adverse reactions (occurring in ≥20% of patients) were rash, paronychia, musculoskeletal pain, dyspnea, nausea and vomiting, fatigue, edema, stomatitis, cough, and constipation. The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.
Modeling Posttreatment Prognosis of Skin Lesions in Patients With Psoriasis in China
Authors: Zhihui Yang, Shasha Han, Peng Wu, Mingyue Wang, Ruoyu Li, Xiao-Hua Zhou, Hang Li
Journal: JAMA Network Open (2023)

Understanding the posttreatment prognosis of skin lesions in patients with psoriasis is essential for improving patients' treatment satisfaction.To model the prognosis of skin lesions for patients with psoriasis after 3 types of therapy.This prospective cohort study included patients with psoriasis who visited a dermatologist and were enrolled in the platform of the Psoriasis Standardized Diagnosis and Treatment Center in China from August 2020 to December 2021.Biologic, traditional, and systemic therapy for psoriasis.Skin lesions were measured by the Investigator's Global Assessment (IGA) scale subsumed into 4 stages of severity (IGA 0/1, IGA 2, IGA 3, and IGA 4), with higher scores indicating higher severity. The matching method was used to balance baseline covariates between patients receiving each of the 3 treatments. Transition probabilities from IGA scores at baseline to 0 to 1 month and 1 to 12 months were estimated.A total of 8767 patients were included in the final analysis (median age, 38.6 years [IQR, 28.7-52.8 years]; 5809 [66.3%] male). Across the 3 therapies, as the follow-up duration increased, the probability of improvement transition into a less severe IGA stage (from IGA 4 to IGA 0/1) increased from 0.19 (95% CI, 0.18-0.21) in 0 to 1 month to 0.36 (95% CI, 0.34-0.37) in 1 to 12 months. Biologic therapy was associated with greater improvement transitions for severe conditions, with transition probabilities from IGA 4 to IGA 0/1 increasing by 0.06 (95% CI, 0.02-0.09) vs traditional therapy and by 0.06 (95% CI, 0.03-0.09) vs systemic therapy in 0 to 1 month and by 0.08 (95% CI, 0.04-0.12) vs traditional therapy and 0.11 (95% CI, 0.07-0.14) vs systemic therapy in 1 to 12 months.This cohort study modeling psoriasis prognosis provided a complete prognosis of skin lesions, and biologic therapy was associated with improved prognosis of moderate to severe psoriasis compared with traditional and systemic therapies. The study provides insight on using transition diagrams to assess psoriasis prognosis and to communicate with patients in clinical practice.
Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer
Authors: Chad Tang, Alexander D. Sherry, Cara Haymaker, Tharakeswara Bathala, Suyu Liu, Bryan Fellman, Lorenzo Cohen, Ana Aparicio, Amado J. Zurita, Alexandre Reuben, Enrica Marmonti, Stephen G. Chun, Jay P. Reddy, Amol Ghia, Sean McGuire, Eleni Efstathiou, Jennifer Wang, Jianbo Wang, Patrick Pilie, Craig Kovitz, Weiliang Du, Samantha J. Simiele, Rachit Kumar, Yerko Borghero, Zheng Shi, Brian Chapin, Daniel Gomez, Ignacio Wistuba, Paul G. Corn
Journal: JAMA Oncology (2023)

Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial.
Efficacy and Safety of Nivolumab Plus Ipilimumab vs Nivolumab Alone for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Kevin J. Harrington, Robert L. Ferris, Maura Gillison, Makoto Tahara, Athanasios Argiris, Jérôme Fayette, Michael Schenker, Åse Bratland, John W. T. Walker, Peter Grell, Caroline Even, Christine H. Chung, Rebecca Redman, Alexandre Coutte, Sébastien Salas, Cliona Grant, Sergio de Azevedo, Denis Soulières, Aaron R. Hansen, Li Wei, Tariq Aziz Khan, Karen Miller-Moslin, Mustimbo Roberts, Robert Haddad
Journal: JAMA Oncology (2023)

There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Effect of the Communities That Care Prevention System on Adolescent Handgun Carrying
Authors: Ali Rowhani-Rahbar, Sabrina Oesterle, Emma L. Gause, Margaret R. Kuklinski, Alice M. Ellyson, Julia P. Schleimer, Kimberly Dalve, Elizabeth H. Weybright, John S. Briney, J. David Hawkins
Journal: JAMA Network Open (2023)

Importance There is little information on upstream community-based interventions that reduce the prevalence of handgun carrying among adolescents, especially those growing up in rural areas. Objective To test whether Communities That Care (CTC), a community-based prevention system focusing on risk and protective factors for behavioral problems early in life, reduces handgun carrying prevalence among adolescents growing up in rural areas. Design, Setting, and Participants Community-randomized trial of 24 small towns in 7 states assigned randomly to the CTC or control group with outcomes assessed from 2003 to 2011. Participants were youths attending public schools in grade 5 who received consent from their parents to participate (77% of the eligible population) and were repeatedly surveyed through grade 12 with 92% retention. Analyses were conducted from June to November 2022. Interventions A coalition of community stakeholders received training and technical assistance to install CTC, used local epidemiologic data to identify elevated risk factors and low protective factors for adolescent behavioral problems, and implemented tested preventive interventions for youth, their families, and schools. Main Outcomes and Measures Handgun carrying (never vs at least once) operationalized in 2 ways: (1) prevalence of past-year handgun carrying, and (2) cumulative prevalence of handgun carrying from grade 6 through grade 12. Results Overall, the 4407 study participants’ mean (SD) age was 12 (.4) years in both CTC (2405 participants) and control (2002 participants) communities in grade 6; about one-half of participants in each group were female (1220 [50.7 %] in the CTC group and 962 [48.1%] in the control group). From grade 6 through grade 12, 15.5% of participants in CTC communities and 20.7% of those in control communities reported carrying a handgun at least once. Youths in CTC communities were significantly less likely to report handgun carrying at a given grade than those in control communities (odds ratio [OR], 0.73; 95% CI, 0.65-0.82). The most pronounced effects were observed in grade 7 (OR, 0.70; 95% CI, 0.42-0.99), grade 8 (OR, 0.58; 95% CI, 0.41-0.74), and grade 9 (OR, 0.65; 95% CI, 0.39-0.91). Cumulatively from grade 6 through grade 12, youths in CTC communities were significantly less likely to report handgun carrying at least once than those in control communities (OR, 0.76; 95% CI, 0.70-0.84). Overall, CTC reduced the prevalence of past-year handgun carrying by 27% at a given grade and by 24% cumulatively through grade 12. Conclusions and Relevance In this study, CTC reduced the prevalence of adolescent handgun carrying in participating communities. Trial Registration ClinicalTrials.gov Identifier: NCT01088542
Somatic Exonic Deletions in <i>RUNX1</i> Constitutes a Novel Recurrent Genomic Abnormality in Acute Myeloid Leukemia
Authors: Anna Eriksson, Marie Engvall, Lucy Mathot, Albin Österroos, Martin Rippin, Lucia Cavelier, Claes Ladenvall, Panagiotis Baliakas
Journal: Clinical Cancer Research (2023)

In acute myeloid leukemia (AML), somatic mutations (commonly missense, nonsense, and frameshift indels) in RUNX1 are associated with a dismal clinical outcome. Inherited RUNX1 mutations cause familial platelet disorder. As approximately 5%-10% of germline RUNX1 mutations are large exonic deletions, we hypothesized that such exonic RUNX1 aberrations may also be acquired during the development of AML.Sixty patients with well-characterized AML were analyzed with multiplex ligation-dependent probe amplification (n = 60), microarray (n = 11), and/or whole-genome sequencing (n = 8).In total, 25 (42% of the cohort) RUNX1-aberrant patients (defined by the presence of classical mutations and/or exonic deletions) were identified. Sixteen patients (27%) carried only exonic deletions, 5 (8%) carried classical mutations, and 4 (7%) carried both exonic deletions and mutations. No significant difference was observed between patients with classical RUNX1 mutations and RUNX1 exonic deletions in median overall survival (OS, 53.1 vs. 38.8 months, respectively, P = 0.63). When applying the European Leukemia Net (ELN) classification including the RUNX1-aberrant group, 20% of the patients initially stratified as intermediate-risk (5% of the whole cohort) were reassigned to the high-risk group, which improved the performance of ELN classification regarding OS between intermediate- and high-risk groups (18.9 vs. 9.6 months, P = 0.09).Somatic RUNX1 exonic deletions constitute a novel recurrent aberration in AML. Our findings have important clinical implications regarding AML classification, risk stratification, and treatment decision. Moreover, they argue in favor of further investigating such genomic aberrations not only in RUNX1 but also in other genes implicated in cancer biology and management. See related commentary by Chakraborty and Stengel, p. 2742.
Guanidine-modified nanoparticles as robust BTZ delivery carriers and activators of immune responses
Authors: Xiaodan Xu, Rui Wang, Dongdong Li, Jiajia Xiang, Wei Zhang, Xueying Shi, Hongxia Xu, Shasha Yao, Jiwei Liu, Shiqun Shao, Zhuxian Zhou, Feihe Huang, Youqing Shen, Jianbin Tang
Journal: Journal of Controlled Release (2023)
Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions
Authors: Eileen S. Carpenter, Ahmed M. Elhossiny, Padma Kadiyala, Jay Li, Jake McGue, Brian D. Griffith, Yaqing Zhang, Jacob Edwards, Sarah Nelson, Fatima Lima, Katelyn L. Donahue, Wenting Du, Allison C. Bischoff, Danyah Alomari, Hannah R. Watkoske, Michael Mattea, Stephanie The, Carlos E. Espinoza, Meredith Barrett, Christopher J. Sonnenday, Nicholas Olden, Chin-Tung Chen, Nicole Peterson, Valerie Gunchick, Vaibhav Sahai, Arvind Rao, Filip Bednar, Jiaqi Shi, Timothy L. Frankel, Marina Pasca di Magliano
Journal: Cancer Discovery (2023)

Abstract The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions in most individuals irrespective of age. Using a combination of multiplex IHC, single-cell RNA sequencing, and spatial transcriptomics, we provide the first-ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis. Significance: Precursor lesions to pancreatic cancer are poorly characterized. We analyzed donor pancreata and discovered that precursor lesions are detected at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell-intrinsic factors that restrain or, conversely, promote malignant progression. See related commentary by Hoffman and Dougan, p. 1288. This article is highlighted in the In This Issue feature, p. 1275
Forgotten but not gone: Yersinia infections in England, 1975 to 2020
Authors: Dana Šumilo, Nicola K Love, Rohini Manuel, Girija Dabke, Karthik Paranthaman, Claire Jenkins, Noel D McCarthy
Journal: Eurosurveillance (2023)

Background Yersiniosis is one of the most common food-borne zoonoses in Europe, but there are large variations in the reported incidence between different countries. Aim We aimed to describe the trends and epidemiology of laboratory-confirmed Yersinia infections in England and estimate the average annual number of undiagnosed Yersinia enterocolitica cases, accounting for under-ascertainment. Methods We analysed national surveillance data on Yersinia cases reported by laboratories in England between 1975 and 2020 and enhanced surveillance questionnaires from patients diagnosed in a laboratory that has implemented routine Yersinia testing of diarrhoeic samples since 2016. Results The highest incidence of Yersinia infections in England (1.4 cases per 100,000 population) was recorded in 1988 and 1989, with Y. enterocolitica being the predominant species. The reported incidence of Yersinia infections declined during the 1990s and remained low until 2016. Following introduction of commercial PCR at a single laboratory in the South East, the annual incidence increased markedly (13.6 cases per 100,000 population in the catchment area between 2017 and 2020). There were notable changes in age and seasonal distribution of cases over time. The majority of infections were not linked to foreign travel and one in five patients was admitted to hospital. We estimate that around 7,500 Y. enterocolitica infections may be undiagnosed in England annually. Conclusions Findings suggest a considerable number of undiagnosed yersiniosis cases in England, with possibly important changes in the epidemiology. The apparently low incidence of yersiniosis in England is probably due to limited laboratory testing.
Letter concerning “Novel intra-operative strategies for enhancing tumour control: Future directions”
Authors: Oscar James MacCormac
Journal: Neuro-Oncology (2023)

Journal Article Letter concerning "Novel intra-operative strategies for enhancing tumour control: Future directions" Get access Oscar James MacCormac Oscar James MacCormac School of Biomedical Engineering and Imaging Sciences, King's College London, UKDepartment of Neurosurgery, King's College Hospitals NHS Foundation Trust, London, UK Corresponding Author: Oscar James MacCormac, MD, King's College London, 9th Floor Becket House, London, SE1 7EH, UK (oscar.j.maccormac@kcl.ac.uk). https://orcid.org/0000-0002-2938-543X Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 6, June 2023, Page 1196, https://doi.org/10.1093/neuonc/noad056 Published: 06 April 2023 Article history Corrected and typeset: 06 April 2023 Published: 06 April 2023